Spacer devices for metered dose inhalers

Spacer devices are attachments to the mouthpieces of pressurised metered dose inhalers (pMDIs), and range from tube spacers with a volume of <50 mL to holding chambers with a volume of 750 mL. Compared with a pMDI alone, spacers minimise coordination difficulties, reduce oropharyngeal deposition and often increase lung deposition. Spacers may not improve the clinical effect in patients able to use a pMDI properly, but may allow maintenance dosages of bronchodilators and corticosteroids to be reduced. Correct use of spacer devices is important, especially achieving control over electrostatic charge accumulation on the walls of plastic devices. In patients with severe acute asthma or severe chronic obstructive pulmonary disease, a pMDI plus large volume spacer may be a viable alternative to a nebuliser for delivering large bronchodilator doses. Although the addition of a spacer to every pMDI would not be justified, the use of large volume spacers has been recommended for any inhaled asthma drug in young children, and as a means of reducing systemic bioavailability of inhaled corticosteroids in adults and children alike.     

Use of spacers for patients treated with pressurized metered dose inhalers: focus on the VENTOLIN™ Mini Spacer

Introduction: Spacers offer a multitude of benefits by reducing the requirement to coordinate inhalation with actuation and improving inhaler technique in patients using a pressurized metered dose inhaler (pMDI). Spacers improve drug targeting by retaining within the spacer large particles normally deposited in the oropharynx, and by creating a prolonged aerosol cloud of fine particles to give the user increased time to inhale after actuation. This is particularly important in young children and the elderly to effectively deliver medication to the airways.

Areas covered: By investigating the history and features of spacers, we demonstrate that the advantages of using spacers far outweigh their limitations. We also discuss the optimal characteristics of spacers in terms of shape, volume, presence of valve and static charge, and present a detailed discussion of the VENTOLIN? Mini Spacer.

Expert opinion: Generally, the shape and size of spacers makes them inherently inconvenient. Consideration of human factors and modern design may make them more attractive to patients. However, the incentive to use spacers should be their ability to help patients correctly use inhaled medications delivered by pMDIs. Understanding of these principles through education is key to their acceptance by patients.     

Recent advances in aerosol therapy for children with asthma.

Inhalational drug delivery is the primary mode of asthma therapy in children and is the main focus of this article. Pressurized metered dose inhalers (pMDIs) are now the method of choice in infants and children under 5 years old, when used in combination with an appropriate valved holding chamber or spacer. Spacers are particularly important for steroid inhalation to maximize lung deposition and minimize unwanted oropharyngeal deposition. Optimal inhalation technique with a pMDI-spacer in infants is to inhale the drug by breathing tidally through the spacer. Drug delivery to the lungs using pMDIs can vary greatly, depending on the formulation used and the age of the child. Dry powder inhalers (DPIs) are driven by the peak inspiratory flow of the patient and are usually not appropriate for children under 5 or 6 years of age. Nebulizers continue to play a role in the treatment of acute asthma where high doses of bronchodilator are required, though multiple doses via pMDI spacer may suffice. Important drug delivery issues specific to children include compliance, use of mask versus mouthpiece, lower tidal volumes and inspiratory flows, determination of appropriate dosages, and minimization of adverse local and systemic effects.     

Comparing the efficacy and safety of salmeterol/fluticasone pMDI versus its mono-components,other LABA/ICS pMDIs and salmeterol/fluticasone Diskus in patients with asthma

Introduction: Pressurized metered dose inhalers (pMDIs) are evolving to be a very effective drug delivery option in patients with airway diseases. They offer comparable lung deposition and reduced oropharyngeal deposition similar with the dry powder inhalers. As recommended by the Global Initiative for Asthma guidelines, the ideal maintenance treatment for asthma is a combination of long acting β₂-agonists (LABAs) and inhaled corticosteroids (ICSs). One of the available LABA/ICS combinations is the salmeterol/fluticasone propionate combination (SFC) and a plethora of evidence supports its clinical efficacy and safety.

Areas covered: This article focuses on the SFC hydrofluroalkane pMDI and compares the efficacy and tolerability with salmeterol and fluticasone given individually, and with other fixed-dose combinations namely formoterol/fluticasone, formoterol/beclometasone and formoterol/mometasone furoate, all delivered via pMDI. Also discussed is the efficacy and tolerability of the SFC delivered via a pMDI, as compared to the SFC via Diskus.

Expert opinion: pMDIs play an important role in inhalation therapy given the low price, low maintenance and convenience of use. LABA/ICS combinations are the preferred choice of medication for asthma treatment and will remain the mainstay for the decades to come. In our opinion, pMDI should be the choice of device to administer LABA/ICS maintenance therapy, as it is already being used by the patients for reliever therapy, which may eventually improve patient adherence and compliance.     

Comparison of beclomethasone dipropionate delivery by easyhaler dry powder inhaler and pMDI plus large volume spacer.

Dry powder inhalers (DPIs) provide a means of delivering inhaled asthma drugs without the use of propellants. Easyhaler is a multidose DPI, delivering 200 doses of beclomethasone dipropionate (BDP), 200 microg/dose. A gamma scintigraphic study has been carried out in 10 healthy volunteers to compare the deposition of BDP from Easyhaler with that from a pressurized metered dose inhaler (pMDI) coupled to a Volumatic spacer device delivering 250 microg BDP per dose. The spacer was used without any pretreatment to reduce static charge on the spacer walls. The study was conducted according to an open, randomized, crossover design. The volunteers inhaled the study drug using optimal inhalation technique for both devices. Lung deposition of 99mTc-labeled BDP averaged 18.9% (SD 9.5%) of the metered dose for Easyhaler, and 11.2% (SD 5.3%) for pMDI plus spacer (p < 0.05); when the data were expressed as mass of BDP deposited in the lungs, the difference in lung deposition just failed to reach statistical significance (Easyhaler 37.8 microg; pMDI plus spacer 28.0 microg). Oropharyngeal deposition was significantly reduced by use of the spacer. The results of this study show that Easyhaler delivers drug more efficiently to the lungs than pMDI plus Volumatic spacer when no measures are taken to eliminate static charge on the spacer walls.     

Comparison of Gamma Scintigraphy and a Pharmacokinetic Technique for Assessing Pulmonary Deposition of Terbutaline Sulphate Delivered by Pressurized Metered Dose Inhaler

A comparison has been made of pulmonary deposition of terbutaline sulphate from a pressurized metered dose inhaler (pMDI), measured in 8 healthy male subjects by gamma scintigraphy and by a pharmacokinetic (charcoal-block) method, involving drug recovery in urine. Measurements were carried out with a pMDI at slow (27 1/min) and fast (151 1/min) inhaled flows and with Nebuhaler^® large volume spacer device (average inhaled flow 171/min). Overall, the two methods did not differ significantly in their estimates of whole lung deposition, although values obtained by gamma scintigraphy exceeded those from the charcoal-block method for the pMDI with fast inhalation. The regional distribution of drug within the lungs and deposition in the oropharynx could be assessed by gamma scintigraphy, but not by the charcoal-block method. It is concluded that either method may be used to assess whole lung deposition of terbutaline sulphate from pMDIs, both with and without a spacer, although each method has its own inherent advantages and disadvantages.     

Use of inhaler devices in pediatric asthma

Inhalation is the preferred route for asthma therapy, since it offers a rapid onset of drug action, requires smaller doses, and reduces systemic effects compared with other routes of administration. Unfortunately, inhalation devices are frequently used in an empirical manner rather than on evidence-based awareness.A wide variety of nebulizers are available. Conventional jet nebulizers are highly inefficient, as much of the aerosol is wasted during exhalation. However, incorporating an extra open vent into the system has considerably increased the amount of drug that patients receive. Breath-assisted open vent nebulizers limit the loss of aerosol during exhalation, but are dependent on the patient's inspiratory flow. Ultrasonic nebulizers produce a high mass output and have a short nebulization time, but are inefficient for delivering suspensions or viscous solutions. Adaptive aerosol delivery devices release a precise dose that is tailored to the individual patient's breathing pattern. Nebulizers have several drawbacks, and their use should be limited to patients who cannot correctly manage other devices.Pressurized metered-dose inhalers (pMDI) are practical, cheap and multidose. However, there are several problems with their use. Breath-actuated MDI are easy to use and can be activated by very low flow. However, young children may not be able to use them efficiently. Dry powder inhalers (DPI) are portable and easy to use. They are indicated either for rescue bronchodilator therapy or for regular treatment with inhaled corticosteroids and long-acting bronchodilators. The use of spacers reduces oropharyngeal deposition and improves drug delivery to the lung. Spacers do not require patient coordination, but some general rules must be followed for their optimal use.Thus, the choice of a delivery device mainly depends on the age of the patient, the drug to be administered and the condition to be treated. Proper education is also essential when prescribing an inhalation device.     

Intra-subject variability in lung dose in healthy volunteers using five conventional portable inhalers.

High intra-subject variability in lung dose achieved when using aerosol delivery systems may impact on the efficacy of treatment in clinical practice. While the dose delivered by metered dose inhalers (pMDIs) is highly reproducible when tested in vitro, the variability in dose delivered to the lungs is known to be high. It has been suggested that newer delivery systems such as dry powder inhalers (DPIs) or breath actuated pMDIs significantly reduce the intra-subject variability in lung dose, but this remains untested. The 30-min urinary salbutamol technique was used to assess intra-subject variability in lung dose for five portable inhaler devices. Thirteen healthy adult subjects inhaled salbutamol from five different devices. Each device was used at five separate study days, a total of 25 visits. The devices studied were the Evohaler pMDI, a pMDI with Volumatic (pMDI + HC), the Easibreath, the Accuhaler and the Turbohaler. Subjects inhaled 400 microg of salbutamol and produced a urine sample exactly 30 min later. Quantities of salbutamol contained in the urine were determined using an HPLC technique. The mean coefficient of variation (CV% and range) for lung dose were 31.8% (20.1-87.4) for the pMDI + HC, Easi-breathe 35.9% (10.4-66.2), Accuhaler 40.4% (15.6-75.2), Turbohaler 42.4% (20.7-74.2), and 52.0% (27.1-49.3) for the pMDI alone. There was no significant statistical significant difference between any of the devices. In seven of 13 subjects, the greatest lung dose was achieved with the Volumatic. The observed intra-subject in health volunteers is similar to the reported intra-subject variability of bioavailability for a number of oral medications. Though there was trend towards higher variability when using the pMDI, this was not statistically significant and was largely attributable to one subject in with a poor technique.     

Novolizer: how does it fit into inhalation therapy?

Inhalation therapy is the preferred route of administration of anti-asthmatic drugs to the lungs. However, the vast majority of patients cannot use their inhalers correctly, particularly pressurised metered dose inhalers (pMDIs). The actual proportion of patients who do not use their inhalers correctly may even be under-estimated as GPs tend to over-estimate correct inhalation technique. Dry powder inhalers (DPIs) have many advantages over pMDIs. Unlike pMDIs, they are environmentally-friendly, contain no propellant gases and, more importantly, they are breath-activated, so that the patient does not need to coordinate actuation of the inhaler with inspiration. Three key parameters for correct inhaler use should be considered when evaluating existing or future DPI devices and especially when choosing the appropriate device for the patient: (1) usability, (2) particle size distribution of the emitted drug and (3) intrinsic airflow resistance of the device. The Novolizer is a breath-activated, multidose, refillable DPI. It is easy to use correctly, has multiple feedback and control mechanisms which guide the patient through the correct inhalation manoeuvre. In addition, the Novolizer has an intelligent dose counter, which resets only after a correct inhalation and may help to monitor patient compliance. The Novolizer has a comparable or better lung deposition than the Turbuhaler at similar or higher peak inspiratory flow (PIF) rates. A flow trigger valve system ensures a clinically effective fine particle fraction (FPF) and sufficient drug delivery, which is important for a good lung deposition. The FPF produced through the Novolizer is also relatively independent of flow rate and the device shows better reproducibility of metering and delivery performance compared to the Turbuhaler. The low-to-medium airflow resistance means that the Novolizer is easy for patients to use correctly. Even children, patients with severe asthma and patients with moderate-to-severe chronic obstructive pulmonary disease (COPD) have no problems to generate the trigger inspiratory flow rate required to activate the Novolizer. The Novolizer uses an advanced DPI technology and may improve patient compliance.     

Computational analyses of a pressurized metered dose inhaler and a new drug-aerosol targeting methodology.

The popular pressurized metered dose inhaler (pMDI), especially for asthma treatment, has undergone various changes in terms of propellant use and valve design. Most significant are the choice of hydrofluoroalkane-134a (HFA-134a) as a new propellant (rather than chlorofluorocarbon, CFC), a smaller exit nozzle diameter and attachment of a spacer in order to reduce ultimately droplet size and spray inhalation speed, both contributing to higher deposition efficiencies and hence better asthma therapy. Although asthma medicine is rather inexpensive, the specter of systemic side effects triggered by inefficient pMDI performance and the increasing use of such devices as well as new targeted drug-aerosol delivery for various lung and other diseases make detailed performance analyses imperative. For the first time, experimentally validated computational fluid-particle dynamics technique has been applied to simulate airflow, droplet spray transport and aerosol deposition in a pMDI attached to a human upper airway model, considering different device propellants, nozzle diameters, and spacer use. The results indicate that the use of HFA (replacing CFC), smaller valve orifices (0.25 mm instead of 0.5 mm) and spacers (ID = 4.2 cm) leads to best performance mainly because of smaller droplets generated, which penetrate more readily into the bronchial airways. Experimentally validated computer simulations predict that 46.6% of the inhaled droplets may reach the lung for an HFA-pMDI and 23.2% for a CFC-pMDI, both with a nozzle-exit diameter of 0.25 mm. Commonly used inhalers are nondirectional, and at best only regional drug-aerosol deposition can be achieved. However, when inhaling expensive and aggressive medicine, or critical lung areas have to be reached, locally targeted drug-aerosol delivery is imperative. For that reason the underlying principle of a future line of "smart inhalers" is introduced. Specifically, by generating a controlled air-particle stream, most of the inhaled drug aerosols reach predetermined lung sites, which are associated with specific diseases and/or treatments. Using the same human upper airway model, experimentally confirmed computer predictions of controlled particle transport from mouth to generation 3 are provided.     

Key issues in inhalation therapy in children

In order to achieve asthma control it is essential that children receive the appropriate education and training pertaining to the management of their disease, are prescribed the correct medication according to severity, and most importantly, are prescribed the correct inhaler to ensure medication is deposited in their lungs. There are three major misconceptions which physicians and patients have regarding the use of inhalers in children. Firstly, that the nebulizer is more effective than a pressurised metered dose inhaler (pMDI) plus spacer in treating acute asthma in children. Secondly that using an inhaler correctly is easy, and lastly that correct use of the inhaler, once taught, persists over time. However, recent studies have shown that these conceptions are false. Firstly, comparable efficacy is achieved by treatment with inhaled corticosteroids or bronchodilators delivered through a nebulizer and a pMDI plus spacer, both when used to treat acute asthma and for maintenance therapy. Secondly, contrary to general opinion, using an inhaler correctly is difficult for children. Many children with asthma use their inhaler devices incorrectly, even after instruction for correct use of the inhaler. Thirdly, correct inhalation technique deteriorates over time; and inhalation instructions, therefore, should be given repeatedly to achieve and maintain correct inhalation technique in asthmatic children. The profile of the ideal inhaler comprises good drug deposition in the lower airways, deliverance of a consistent dose, being easy to teach and to use correctly, and being small in size and convenient to handle. It should also be multidose, require a low inspiratory airflow for activation, provide feedback to patients on correct use of the inhaler, be re-usable, have an appealing design and feel, and have a reliable dose counter which may help to monitor the patient's compliance. The Novolizer device, a new multidose dry powder inhaler (DPI), shows many of these characteristics making it potentially very suitable for children with asthma.     

How to achieve good compliance and adherence with inhalation therapy

The correct use of inhaler devices is an inclusion criterion for all studies comparing inhaled treatments. However, in real life patients make many errors when inhaling their medication which may negate the benefits observed in clinical trials. A recently published observational study evaluated inhaler handling in 3811 patients for at least 1 month using the Aerolizer, Autohaler, Diskus, pressurised metered dose inhaler (pMDI) or Turbuhaler devices. Inhalation errors were considered critical if they could have substantially affected drug delivery to the lung. The two most common errors made by patients were device-independent errors and included not breathing out before actuation of the device (28.9%) and failure to breath-hold for a few seconds after inhalation (28.3%). These errors were observed in 40%-47% of patients. The number of patients making at least one error with breath-actuated inhalers was high; with less than 50% of patients inhaling correctly. Seventy-six per cent of patients made at least one error with pMDI compared to 49%-55% with breath-actuated inhalers. With respect to device-dependent errors, the pMDI fared worst with 69% of patients exhibiting at least one error, closely followed by the Turbuhaler (32%) and Autohaler (41%). Critical errors were made by only 11%-12% of patients treated with Aerolizer, Autohaler or Diskus compared to 28% and 32% of patients treated with pMDI and Turbuhaler, respectively. Over-estimation of good inhalation by GPs was maximal for Turbuhaler (24%) and lowest for Autohaler and pMDI (6%). Ninety per cent of GPs felt that participation in the study would improve error detection. Compliance may be improved by educating patients and physicians in the correct use of inhaler devices. Inhalers should be easy to use correctly, and have multiple feedback and control mechanisms which would reduce physician over-estimation of a correct inhalation, allow compliance to be monitored, facilitate patient self-education and give reassurance to patients in the real life setting.     

Determining factors of aerosol deposition for four pMDI-spacer combinations in an infant upper airway model.

The aim of this study was to measure and compare the influence of tidal volume (Vt) respiratory rate (RR) and pMDI/spacer combination on aerosol deposition of 4 pMDI/spacer combinations, which are used for infants. An anatomically correct upper airway model of a 9-month-old infant was connected to a breathing simulator. Sinusoidal breathing patterns were simulated with; duty cycle T(i)/T(tot) = 0.42, Vt: 25, 50, 75, 100, 150, 200 ml (RR: 30 breaths/min); and RR: 20, 30, 42, 60, 78 breaths/min (Vt: 100 mL). pMDI/Spacers tested were: budesonide 200 microg/Nebuchamber, fluticasone 125 microg/Babyhaler and both budesonide and fluticasone with Aerochamber. Plastic spacers were detergent coated to reduce electrostatic charge. Spacer-output and lung dose were measured by a filter positioned between spacer and facemask or between model and breathing simulator. Particle size distribution of lung dose was assessed with an impactor during simulated breathing. Spacer-output was significantly positively correlated with Vt for all pMDI/spacers (all R > 0.77, p < 0.001), but not correlated with RR. Lung doses initially increased from Vt = 25 to 50 mL (Nebuchamber, Aerochamber) or to 100 mL (Babyhaler) and then decreased, with increasing Vt and RR (R: -0.98 to -0.82, p < 0.001). Lung doses of fluticasone were 1.5-6-fold higher compared with budesonide, irrespective of spacer type (p < 0.001). MMAD decreased with increasing Vt and RR. Dose to the lungs of particles <2.1 microm was independent of Vt and RR. Lung dose decreases with increasing inspiratory flow (increasing Vt or RR) by increasing impaction of coarse particles in the upper airways. Deposition of particles <2.1 microm is relatively flow independent. When electrostatic charge of spacers is reduced, lung dose is pMDI dependent and spacer independent.     

Deposition and pharmacokinetics of an HFA formulation of triamcinolone acetonide delivered by pressurized metered dose inhaler.

Novel formulations of asthma drugs contained in pressurized metered dose inhalers (pMDIs) are being developed containing hydrofluoroalkane (HFA) propellants. The objectives of this study were to assess the deposition in the lungs and oropharynx of triamcinolone acetonide (TAA; Azmacort, Aventis Pharma, Collegeville, PA) delivered by pMDI formulated with HFA-134a, together with the pharmacokinetic profile of TAA, and to determine the extent to which the Azmacort spacer improves targeting of TAA to the lungs. The deposition of TAA, labelled with 99mTc, was assessed by gamma scintigraphy in 10 patients with mild to moderate asthma (mean forced expiratory volume in one second [FEV1] 76% predicted), who received in randomized order three delivered (ex-device) doses of 75 microg TAA via pMDI coupled to an Azmacort spacer (TAA-spacer), and three delivered doses of 230 microg TAA via the same device, but with the spacer removed (TAA-no spacer). Mean lung deposition expressed as mass of drug was similar for each regimen (TAA-no spacer 175 microg; TAA-spacer 188 microg), but when expressed as percentage delivered dose, lung deposition was higher for TAA-spacer (53.8%) versus TAA-no spacer (26.0%), indicating superior drug targeting for TAA-spacer. The spacer reduced oropharyngeal deposition. The pharmacokinetic data showed higher plasma levels of drug for TAA-no spacer, resulting from higher oropharyngeal deposition. "Pharmacoscintigraphic" data showed proof of concept for a novel HFA delivery system for an inhaled corticosteroid based on pulmonary targeting of drug.     

Delivery of HFA and CFC salbutamol from spacer devices used in infancy

The aim of the study was to compare the in vitro delivery of four salbutamol pressurized metered-dose inhalers (pMDIs) via the three spacer devices commonly used in European infants: Aerochamber-Infant, Babyhaler, and metallic NES-spacer. Emitted dose (ED) and fine particle dose (FPD, particles<5.8 microm) of each combination of spacer device and pMDI (chlorofluorocarbon-based Ventoline, Eolène, Spréor, and hydrofluoroalkane-based Airomir were measured respectively using unit dose sampling tubes (n=30 per combination) and an 8-stage cascade impactor (n=6 per group). The results were compared by analysis of variance and the Student-Newman-Keuls method. ED of Airomir was always greater than for Ventoline (P<0.05). FPD obtained with Ventoline was the lowest, with Eolène>Airomir=Spréor>Ventoline (P<0.05). Only Airomir produced a similar FPD with all three spacer devices. Chlorofluorocarbon-salbutamol pMDIs are not generics when used with spacer devices. The three spacer devices may be used interchangeably with Airomir.     

The Interaction Between the Oropharyngeal Geometry and Aerosols via Pressurised Metered Dose Inhalers

Purpose  

This study investigated the effect of oropharyngeal geometry on inhaled aerosol characteristics via pressurised metered dose inhalers (pMDIs), both with or without spacers.     

Assessment of handling of inhaler devices in real life: an observational study in 3811 patients in primary care.

The correct use of inhalation devices is an inclusion criterion for all studies comparing inhaled treatments. In real life, however, patients may make many errors with their usual inhalation device, which may negate the benefits observed in clinical trials. Our study was undertaken to compare inhalation device handling in real life. A total of 3811 patients treated for at least 1 month with an inhalation device (Aerolizer, Autohaler, Diskus, pressurized metered dose inhaler (pMDI), or Turbuhaler) were included in this observational study performed in primary care in France between February 1st and July 14th, 2002. General practitioners had to assess patient handling of their usual inhaler device with the help of a checklist established for each inhaler model, from the package leaflet. Seventy-six percent of patients made at least one error with pMDI compared to 49-55% with breath-actuated inhalers. Errors compromising treatment efficacy were made by 11-12% of patients treated with Aerolizer, Autohaler, or Diskus compared to 28% and 32% of patients treated with pMDI and Turbuhaler, respectively. Overestimation of good inhalation by general practitioners was maximal for Turbuhaler (24%), and lowest for Autohaler and pMDI (6%). Ninety percent of general practitioners felt that participation in the study would improve error detection. These results suggest that there are differences in the handling of inhaler devices in real life in primary care that are not taken into account in controlled studies. There is a need for continued education of prescribers and users in the proper use of these devices to improve treatment efficacy.     

Comparison of the aerosol velocity and spray duration of Respimat Soft Mist inhaler and pressurized metered dose inhalers.

Apart from particle size distribution, spray velocity is one of the most important aerosol characteristics that influence lung deposition of inhaled drugs. The time period over which the aerosol is released (spray duration) is also important for coordination of inhalation. Respimat Soft Mist Inhaler (SMI) is a new generation, propellant-free inhaler that delivers drug to the lung much more efficiently than pressurised metered dose inhalers (pMDIs). The objective of this study was to compare the velocity and spray duration of aerosol clouds produced by Respimat SMI with those from a variety of chlorofluorocarbon (CFC) and hydrofluoroalkane (HFA) pMDIs. All inhalers contained solutions or suspensions of bronchodilators. A videorecording method was used to determine the aerosol velocity. For spray duration, the time for generation of the Soft Mist by Respimat SMI was initially determined using three different methods (videorecording [techniques A and B], laser light diffraction and rotating disc). Videorecording was then used to compare the spray duration of Respimat SMI with those from the other inhalers. The Soft Mist produced by Respimat SMI moved much more slowly and had a more prolonged duration than aerosol clouds from pMDIs (mean velocity at a 10-cm distance from the nozzle: Respimat SMI, 0.8 m/sec; pMDIs, 2.0-8.4 m/sec; mean duration: Respimat SMI, 1.5 sec; pMDIs, 0.15-0.36 sec). These characteristics should result in improved lung and reduced oropharyngeal deposition, and are likely to simplify coordination of inhaler actuation and inhalation compared with pMDIs.     

InVitro Evaluation of Optimal Inhalation Flow Patterns for Commercial Dry Powder Inhalers and Pressurized Metered Dose Inhalers With Human Inhalation Flow Pattern Simulator

This study aimed at developing a novel analytical method to identify optimal inhalation flow patterns for commercial dry powder inhalers (DPIs) and pressurized metered dose inhalers (pMDIs). As typical commercial DPI and pMDI, Pulmicort^® Turbuhaler^®, and Sultanol^® Inhaler were evaluated by an in vitro inhalation performance testing system with a flow pattern simulator. An 8-stage Andersen cascade impactor (ACI) or twin stage liquid impinger (TSLI) was applied to determine the inhalation performance. The peak flow rate (PFR) of the inhalation flow pattern was set from 15 to 80 L/min in reference to our previous study. From TSLI test results, a higher PFR improved the inhalation performance of the DPI, while the performance of the pMDI was less affected by the PFR. Conversely, from ACI test results, the pMDI performance decreased with a higher PFR, while the DPI followed a similar pattern as in the TSLI test results, because ACI is a finer aerodynamic classification apparatus than TSLI. These results suggested that our in vitro system using a human inhalation flow pattern simulator successfully detected different optimal inhalation patterns between DPI and pMDI. That is, the higher PFR is better for Pulmicort^® Turbuhaler^® (DPI). Conversely, lower PFR is desirable for Sultanol^® Inhaler (pMDI).